Infantile spasms are seizures characterized by sudden flexion of the arms, forward flexion of the trunk, extension of the legs, and hypsarrhythmia on electroencephalography. Treatment is adrenocorticotropic hormone, oral corticosteroids, or vigabatrin.
Infantile spasms last a few seconds and can recur many times a day. They usually manifest in children < 1 year of age. Seizures may resolve spontaneously by about 5 years of age but are often replaced by other types of seizures.
Pathophysiology is unknown; however, infantile spasms may reflect abnormal interactions between the cortex and brain stem.
Causes of Infantile Spasms
Usually, infantile spasms occur in infants with serious brain disorders and developmental abnormalities that often have already been recognized. These disorders may include
Tuberous sclerosis complex is a common cause; prognosis is sometimes better when seizures are caused by this disorder than when seizures have other identifiable causes.
Sometimes the cause of infantile spasms cannot be identified.
Symptoms and Signs of Infantile Spasms
Spasms begin with a sudden, rapid, tonic contraction of the trunk and limbs, sometimes for several seconds. Spasms range from subtle head nodding to contraction of the whole body. They involve flexion, extension, or, more often, both (mixed). The spasms usually occur in clusters, often several dozen, in close succession and occur typically after children wake up and occasionally during sleep. Sometimes, at first, they are mistaken for startles.
Developmental delays (see Childhood Development) are usually present. In the first stages of the disorder, developmental regression can occur (eg, children may stop smiling or lose the ability to sit up or roll over).
Rate of premature death ranges from 5 to 31% and is related to the etiology of the infantile spasms.
Diagnosis of Infantile Spasms
- Electroencephalography (EEG) with awake and asleep stages
- Neuroimaging, preferably MRI
- Testing to identify the cause unless an underlying significant neurologic disorder has already been identified
Previous history (eg, neonatal hypoxic-ischemic encephalopathy) and/or symptoms and signs suggest the diagnosis of infantile spasms in some children. Physical and neurologic examinations are done, but often no pathognomonic findings are identified except in tuberous sclerosis complex.
EEG is done to confirm the diagnosis and check for specific abnormalities. Typically, the interictal pattern is hypsarrhythmia (chaotic, high-voltage polymorphic delta and theta waves with superimposed multifocal spike discharges). Multiple variations (eg, focal or asymmetric hypsarrhythmia) are possible. The ictal pattern is usually a sudden, marked and diffuse attenuation of electrical activity.
Neuroimaging, preferably MRI, is done if it has not already recently been done.
Tests to determine the cause
If it is not clear from neuroimaging or the previous history, tests to determine the cause may include
- Laboratory tests (eg, complete blood count with differential; measurement of serum glucose, electrolytes, blood urea nitrogen, creatinine, sodium, calcium, magnesium, phosphorus, serum amino acids, and urine organic acids; liver tests) if a metabolic disorder is suspected
- Genetic testing
- Cerebrospinal fluid (CSF) analysis to check for metabolic disorders
Treatment of Infantile Spasms
- Intramuscular adrenocorticotropic hormone (ACTH)
- Oral corticosteroids
- Vigabatrin (especially for tuberous sclerosis complex)
Infantile spasms are not responsive to typical antiseizure drugs.
ACTH is the most effective treatment. Both high-dose (150 units/m2) ACTH and low-dose (20 units/m2) ACTH, given daily IM, have been used. The Pediatric Epilepsy Research Consortium (PERC) recommends the higher dose, given for 2 weeks and then tapered down every 3 days until 29 days of treatment are completed. If low-dose therapy is tried and has not stopped spasms within 2 weeks, the higher dose is used.
Corticosteroids (eg, oral prednisone) are sometimes given for 4 to 7 weeks as an alternative to ACTH. A regimen recommended by PERC uses oral prednisolone as follows:
- Days 1 to 14: 10 mg 4 times a day
- Days 15 to 19: 10 mg 3 times a day
- Days 20 to 24: 10 mg 2 times a day
- Days 25 to 29: 10 mg once a day
Vigabatrin is the drug of choice when the spasms are caused by tuberous sclerosis complex. It is also often used in children with an established preexisting serious brain injury or malformation and in those who do not tolerate or respond to ACTH. Dosage of oral vigabatrin is 25 mg/kg 2 times a day, increased gradually up to 75 mg/kg 2 times a day if needed. There is insufficient evidence that any other antiseizure drug or the ketogenic diet is effective.
In some patients with resistant spasms or with focal cortical malformation, epilepsy surgery can eliminate seizures.
There is evidence that the more quickly effective therapy is initiated, the better the neurodevelopmental outcome, particularly when no cause is identified.
- Knupp KG, Coryell J, Nickels KC, et al: Response to treatment in a prospective national infantile spasms cohort. Ann Neurol 79(3):475–484, 2016. doi: 10.1002/ana.24594
- Infantile spasms last a few seconds and can recur many times a day; they may resolve spontaneously by about 5 years of age but are often replaced by other types of seizures.
- Usually, infantile spasms occur in infants with serious brain disorders and developmental abnormalities that often have already been recognized; tuberous sclerosis complex is a common cause.
- Do electroencephalography to confirm the diagnosis, and other tests (eg, brain MRI and metabolic and genetic testing) to evaluate the cause of infantile spasm.
- Adrenocorticotropic hormone (ACTH) is the most effective treatment, but vigabatrin is the drug of choice for spasms caused by tuberous sclerosis complex and is often used in children who have an established preexisting serious brain injury or malformation or who do not tolerate or respond to ACTH; oral corticosteroids may also be used.
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